Table 3.

Descriptions of Patient Cases

ID	Age	Sex	CV comorbiditiesb	ITRA indication	CV toxicity type	Naranjo Score	Time to ADE (weeks)	ITRA oral dosec	Formulation	ITRA Loadd	ITRA + H-ITRA levele (μg/mL)	Clinician action Regarding ITRA	Resolution
1	70	M	3,5	Pulmonary histoplasmosis	right heart failure, edema	9	6	200 mg BID	capsule	Yes	2	Discontinue	partial
2	67	M		Disseminated histoplasmosis	HTN	8	2	200 mg BID	capsule	Yes	2.9	Discontinue	complete
3	33	M		Disseminated Blastomyces	pleural effusions, pulmonary edema, SOB	8	8	Unknown	liquid	Unknown	6.2	Discontinue	unknown
4	65	M		Pulmonary histoplasmosis	HFpEF, edema	8	2	200 mg BID	liquid	Yes	11.5	Modify dose	complete
5	84	M	3	Pulmonary histoplasmosis and Blastomyces	HTN	8	5	200 mg BID	capsule	Yes	4.3	Discontinue	partial
6	77	M		Pulmonary histoplasmosis	edema, pleural effusion	8	8	200 mg BID	capsule	Unknown	10.1	Discontinue	complete
7	52	F	5	Pulmonary Blastomyces	HTN, edema, hypokalemia, and metabolic acidosis	8	7	100 mg BID	capsule	Yes	7.8	Discontinue	complete
8	68	F	1	Pulmonary Aspergillus	HFpEF, HTN, edema	7	8	200 mg BID	capsule	No	4.8	Modify dose	partial
9	70	F		Pisseminated histoplasmosis	HTN, edema	7	34	200 mg BID	capsule	No	5.9	Discontinue	complete
10	65	M	1,2	Pisseminated Blastomyces	HFpEF, edema, pulmonary edema	7	3	200 mg BID	capsule	Yes	4.8	Discontinue	complete
11	66	F	1	Pulmonary (NOS)	HFpEF, edema	7	1	200 mg BID	capsule	Yes	5.6	Discontinue	complete
12	72	F	1,5,6	Pulmonary Aspergillus	HFpEF, edema	7	3.5	200 mg BID	capsule	No	-	Discontinue	complete
13	69	M	1,6	Penosynovitis (NOS)	HFrEF, edema	7	3	200 mg BID	capsule	No	4.5	Discontinue	complete
14	66	F		Pisseminated Coccidioides	edema	7	1	200 mg BID	capsule	Yes	3.1	Discontinue	complete
15	50	M		Pulmonary histoplasmosis	edema, SOB	7	1.5	200 mg BID	capsule	No	5.9	Discontinue	complete
16	53	F	3,6	Disseminated histoplasmosis	HFrEF, edema	7	4	Unknown	unknown	Unknown	2.3	Discontinue	no resolution
17	63	M		Prophylaxis	HFrEF, edema	7	69	300 mg BID	capsule	Yes	2.5	Discontinue	complete
18	71	F	5	Pulmonary histoplasmosis	HTN, edema	7	4	200 mg BID	capsule	No	5.6	Discontinue	partial
19	57	F		Pulmonary histoplasmosis	edema	6	3	200 mg BID	capsule	Yes	7.5	Continue regimen	no resolution
20	73	M	5	Pulmonary Crytococcus	HFrEF	6	104	200 mg BID	capsule	No	-	Continue regimen	no resolution
21	50	F	1	Pulmonary Coccidioides	edema	6	1	200 mg BID	capsule	Yes	3	Discontinue	complete
22	55	F	1	Disseminated histoplasmosis	HTN, pericardial effusion	6	24	200 mg BID	capsule	Yes	4.3	Modify dose	partial
23	54	M	3	Pulmonary histoplasmosis	edema	6	0.3	200 mg BID	capsule	Yes	-	Discontinue	complete
24	69	M	5	Pulmonary (NOS)	HTN	6	unknown	Unknown	unknown	Unknown	-	Discontinue	complete
25	63	M		Disseminated Blastomyces	edema, nocturia	6	67	200 mg BID	liquid	No	3.5	Modify dose	partial
26	66	F		Pulmonary histoplasmosis	HFrEF	6	4	200 mg QD	liquid	No	2.9	Discontinue	partial
27	73	F	3	Disseminated histoplasmosis	edema	6	104	200 mg BID	capsule	Yes	6.8	Modify dose	no resolution
28	70	M		Disseminated Blastomyces	HFpEF, edema	5	2	200 mg BID	capsule	No	-	Discontinue	partial
29	64	M	5	Disseminated Coccidioides	edema	5	2.5	400 mg BID	capsule	Yes	4.8	Modify dose	partial
30	60	F	1	Tenosynovitis histoplasmosis	HFrEF, cardiac arrest	5	30	100 mg BID	liquid	No	11.7	Discontinue	complete
31	21	M		Disseminated histoplasmosis	edema	5	3	300 mg BID	liquid	Yes	1.8	Discontinue	complete

ADE = adverse drug event; BID = twice daily; CV = cardiovascular; HFrEF = heart failure with reduced ejection fraction (left-ventricular ejection fraction ≤40%); H-ITRA = hydroxy-itraconazole; HTN = hypertension; ID = identification; NOS = not otherwise specified; ITRA = itraconazole; SOB = shortness of breath.

^bDefined risk factors include arrhythmia = 1, cardiomyopathy = 2, coronary artery disease = 3, diabetes = 4, hypertension = 5, or hyperlipidemia = 6.

^cDose at time of adverse drug event.

^d200 mg PO TID for at least 3 days at beginning of therapy.

^eHighest total (itraconazole + hydroxyitraconazole) level recorded.